EP2200675B1 - Procédé servant à déterminer la concentration ionique dans une opération extracorporelle de purification de sang soumis à une anticoagulation au citrate - Google Patents

Procédé servant à déterminer la concentration ionique dans une opération extracorporelle de purification de sang soumis à une anticoagulation au citrate Download PDF

Info

Publication number
EP2200675B1
EP2200675B1 EP08782833.1A EP08782833A EP2200675B1 EP 2200675 B1 EP2200675 B1 EP 2200675B1 EP 08782833 A EP08782833 A EP 08782833A EP 2200675 B1 EP2200675 B1 EP 2200675B1
Authority
EP
European Patent Office
Prior art keywords
citrate
ion concentration
blood
substitution medium
extracorporeal blood
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP08782833.1A
Other languages
German (de)
English (en)
Other versions
EP2200675A1 (fr
Inventor
Martin Brandl
Jens Hartmann
Karin Strobl
Dieter Falkenhagen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zentrum fur Biomedizinische Technologie Der Donau- Universitat Krems
Original Assignee
Zentrum fur Biomedizinische Technologie Der Donau- Universitat Krems
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zentrum fur Biomedizinische Technologie Der Donau- Universitat Krems filed Critical Zentrum fur Biomedizinische Technologie Der Donau- Universitat Krems
Publication of EP2200675A1 publication Critical patent/EP2200675A1/fr
Application granted granted Critical
Publication of EP2200675B1 publication Critical patent/EP2200675B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3424—Substitution fluid path
    • A61M1/3431—Substitution fluid path upstream of the filter
    • A61M1/3434—Substitution fluid path upstream of the filter with pre-dilution and post-dilution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3424—Substitution fluid path
    • A61M1/3437—Substitution fluid path downstream of the filter, e.g. post-dilution with filtrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3455—Substitution fluids
    • A61M1/3458—Substitution fluids having electrolytes not present in the dialysate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3672—Means preventing coagulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3672—Means preventing coagulation
    • A61M1/3675—Deactivation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring

Definitions

  • the invention relates to a device for citrate-anticoagulated extracorporeal blood purification, comprising: an extracorporeal blood purification system with an extracorporeal blood circulation comprising a dialysis unit, a blood feed to the dialysis unit for blood taken from a patient, and a blood drain from the dialysis unit for blood to be returned to the patient a controlled citrate dosing device for supplying citrate at a citrate feed site upstream of the dialysis unit, a controlled substitution medium dosing device for supplying a substitution medium at a substitution medium supply point downstream of the dialysis unit, at least one ion concentration measuring means for measuring divalent cations, and a controller connected to the dehydrating citrate at least one ion concentration measuring means and the citrate metering device and the substitution medium metering device is connected, wherein the controller is adapted to the Controlling the dosage of the substitution medium as a function of a comparison between a desired value range and the ion concentration measured by means of the ion concentration measuring
  • the invention relates to a method for detecting an ion concentration of divalent cations of the blood during a citrate-anticoagulated extracorporeal blood purification, wherein a citrate supply citrate located at an extracorporeal blood circuit upstream of a dialysis unit and a substitution medium supply point located downstream of the dialysis unit a substitution medium be introduced into the extracorporeal blood circulation and the control of the dosage of the substitution medium as a function of a comparison between a desired value range and the measured ion concentration takes place.
  • Heparin The current standard used in the clinical treatment of hemodialysis patients heparin, which is introduced by infusion into the arterial limb of the extracorporeal blood circulation. Heparin, however, can lead to complications such as HIT (Heparin Induced Thrombocytopenia) _ [ Hetzel GR, Sucker C (2005), Nephrol Dial Transplant, 20 (10): 2036-2042 ; M. Franchini (2005), Thrombosis Journal, 3 (14 )], Heparin binding to the adsorber or filter, or unwanted intracorporeal anticoagulation, the latter being particularly problematic in patients at increased risk of bleeding.
  • HIT Heparin Induced Thrombocytopenia
  • Used concentrations range from 2 to 7.4 mmol citrate per liter of blood [ Palsson R, Niles JL (1999), Kidney Int 55: 1991-1997 ; Böhler et al. (1996), J Am Soc of Nephrol. 7 (2), 234-241 ], with concentrations of ionized calcium ranging from 0.25 mmol / l to 0.35 mmol / l [ Kutsogiannis et al. (2000), Am J Kidney Dis, Vol. 35, 802-811 ; Tolwani et al. (2001), Kidney International, Vol. 60, 370-374 ] or ⁇ 0.4 mmol / l [ Swartz et al. (2004), Clinical Nephrology, Vol. 61 (2), 134-143 ] can be specified as target values.
  • An extracorporeal blood circulation consists essentially of a filter unit, a blood feed from the patient to the filter unit (arterial leg) and a blood drain from the filter unit to the patient (venous leg).
  • the blood is pumped through the circulation by means of a blood pump.
  • the blood flow [ml / min], as described below, is an important parameter for the system and represents the volume of blood pumped by the blood pump per unit of time.
  • the filter unit usually includes a dialysis filter, a plasma filter or a hemofilter or a combination of them.
  • the membrane blood purification methods are based on the physical processes of diffusion and convection. In the dialysis filter is a semi-permeable membrane that separates the blood from the dialysis fluid.
  • low-molecular substances diffuse out of the blood into the dialysis fluid and are thereby removed from the blood.
  • the extent of the removal of the substances is referred to as clearance and depends on the dialysis filter as well as blood and dialysate flow.
  • the patient can also be deprived of fluid accumulated in the body by means of transmembrane pressure. This process is also referred to as ultrafiltration.
  • filtrate is attached to an ultrafiltration membrane pressed and replaced by substitution solution. The filtrate contains - depending on the filter used - low molecular weight or low and high molecular weight substances.
  • the Citratzuschreib carried out by means of an infusion into the arterial limb of the extracorporeal blood circulation.
  • the blood thus inhibited in its coagulation is purified in membrane or membrane / adsorption-based systems.
  • the citrate and the citrate-calcium complex are removed by dialysis, depending on the dialysis filter used for the most part from the extracorporeal blood circulation, so that only a small portion of the infused citrate enters the bloodstream of the patient.
  • a dialysis unit is advantageous for citrate anticoagulation.
  • Citrate is metabolized in the human body to CO 2 and water, whereby the citrate load of the patient may not substantially exceed the metabolic rate in order to avoid a pathophysiologically relevant effect on the acid / base balance.
  • a calcium-containing or a calcium- and magnesium-containing substitution medium is introduced either by infusion into the venous limb of the extracorporeal blood circulation or via a separate venous access into the blood.
  • citrate anticoagulation is that - in contrast to heparin anticoagulation - the blood clotting is inhibited only in the extracorporeal circulation and unwanted intracorporeal bleeding thereby be avoided.
  • a citrate supplement significantly improves the biocompatibility of an extracorporeal blood purification system because complement activation, which requires the presence of free calcium and magnesium ions, is suppressed by complexing these ions.
  • citrate anticoagulation may be used in patients contraindicated for heparin anticoagulation (HIT). By extended Filter service life when using citrate anticoagulation is particularly suitable for long-term treatments such as in acute dialysis.
  • citrate anticoagulation is slightly more expensive than the heparin method and on the other hand, it is due to the complexity of the dosage and the lack of automation and standardization with a Security risk, requires careful monitoring and is therefore carried out exclusively by experienced experts. If the extracorporeal blood flow changes, the citrate and substitution medium delivery rates must be adjusted manually. Incorrect dosage, caused for example by operator error, incorrect delivery rate adjustment or infusion pump failure, can lead to complications such as hypocalcaemia.
  • the dosage should be adjusted based on the determined ion concentration of the patient's blood - advantageously the calcium ion concentration. Only by a very accurate and very close-meshed or continuous measurement of the calcium ion concentration of the blood, by which a likewise close-meshed or continuous adjustment of the dosage of the infusion solutions is made, the risk of unwanted unphysiological state can be minimized and the safety of the patient can be ensured.
  • WO 91/06326 presented a dialysis procedure with citrate anticoagulation for use in hemodialysis.
  • the citrate is infused into the arterial limb of the extracorporeal blood circulation, the citrate feed rate being adjusted as a function of the blood flow rate.
  • Calcium ions are substituted via a separate venous access, the delivery rate of the Ca-ion substitution solution being adjusted by the citrate feed rate and blood samples taken at several hourly intervals.
  • a close or continuous monitoring of the Ca ion concentration takes place in the WO 91/06326 not described, and it can therefore, as already stated above, the safety of the patient can not be fully guaranteed.
  • the lack of standardization and automation is additionally highly limiting for patient safety and a user-friendly application of the system.
  • a device and a method for the citrate-anticoagulated extracorporeal blood purification is the US 2007/066928 A1 refer to.
  • the document discloses a means for detecting an ion concentration which inter alia measures divalent cations such as calcium and magnesium ions and is located downstream of the dialysis unit in the extracorporeal blood circulation.
  • the dosage of citrate-containing solutions, which can be infused into the extracorporeal blood circulation before and after the dialysis unit is regulated as a function of the measured ion concentration.
  • the dosage of the calcium and magnesium-containing electrolyte solution is independent of the measured ion concentration.
  • the blood purification system has a disposable sensor with which, among other things, calcium can be measured.
  • Another device and method for extracorporeal blood purification without citrate anticoagulation is in the EP 1 175 917 disclosed.
  • DE 101 14 283 C2 discloses a method for determining the ion concentration of the blood of a patient in the citrate-anticoagulated hemodialysis and / or hemofiltration of the type mentioned.
  • the ions are preferably calcium and / or magnesium ions, preferably calcium ions being determined.
  • Fig.1 is shown a suitable device for this purpose, which also from the DE 10114 283 C2 has become known.
  • the device has a hemodialyzer and / or hemofilter 101 and an extracorporeal blood circulation 102, which includes an arterial inflow 103 (arterial limb) from the patient to the hemodialyzer and / or hemofilter 101 and a venous drain 104 (venous limb) from the hemodialyzer and / or hemofilter 101 to the patient.
  • an arterial inflow 103 arterial limb
  • a venous drain 104 venous limb
  • the device has a dialysate line 107, which in turn has a dialysate inlet 108 and a dialysate outlet 109.
  • the ion concentration of the blood is determined indirectly based on the ion concentration in the dialysate 109.
  • there is at least one means for detecting an ion concentration 110 in the dialysate outlet 109 which may be, for example, an ion-sensitive sensor.
  • This ion concentration detection means 110 is connected to a control unit and to the citrate and / or the substitution medium supply means.
  • the ions must be present in the dialysate in uncomplexed form.
  • One possibility is a temporary interruption of citrate infusion into the bloodstream.
  • the other possibility is the release of the ion from the ion-citrate complex, for example by changing the pH by infusion of acid 111 into the dialysate outflow 109 upstream of the means for detecting an ion concentration 110.
  • the big advantage of the method of DE 10114 283 C2 is that for the determination of the ion concentration of the blood no intervention in the blood-side part of the extracorporeal tube system is needed. This is offset by the following disadvantages.
  • a very close-meshed and advantageously continuous determination of the ion concentration of the patient's blood as accurately as possible is necessary for a course of the citrate anticoagulation which ensures the safety.
  • a brief interruption of the addition of citrate to determine the concentration of the blood in the blood according to the one in DE 101 14 283 C2 Accordingly, the procedure described allows only a discontinuous monitoring of the ion concentration and consequently a discontinuous control of anticoagulation. Even with a short-term interruption of Citratzucht can not be fully ensured that adequate anticoagulation can be guaranteed.
  • the ion concentration of the blood on the basis of the concentration in the dialysate, it must be determined in accordance with the procedure given in DE 10114 283 C2 disclosed methods of blood and dialysate flow are included, since the dialysate flow during treatment is usually greater than the blood flow and thus the ion concentration of the blood does not correspond to that of the dialysate.
  • the determination of the ion concentration of the blood can be done either mathematically, but this does not allow accurate determination, or advantageously - because only then is a more accurate determination possible - by reducing the dialysate and a concomitant adjustment of the ion concentration of the dialysate to those of the blood.
  • a lowering of the dialysate flow has the disadvantage that the dialysis efficiency is lowered during this time.
  • certain patient groups eg patients with liver diseases
  • there is a risk of intracorporeal accumulation of citrate if the dialysate flow and thus also the effective citrate clearance are reduced with continuous citrate infusion.
  • a reduction in the dialysate flow prolongs dialysis duration for the patient and, in economic terms, results in an increased use of resources.
  • an accurate and at the same time very close-meshed or advantageously continuous determination of the ion concentration of the blood in continuous continuous dialysis with the method in DE 101 14 283 C2 not feasible.
  • automation and standardization of citrate anticoagulation are difficult due to the complexity of the system.
  • the invention arose within the framework of a research project involving the Center for Biomedical Technology of the Danube University Krems.
  • the goal of the project is to develop an automated online citrate calcium anticoagulation system for easy and safe use.
  • “Online” means continuous regulation of the patient's calcium level using a sensor and adjusting citrate and calcium infusion rates.
  • the calcium infusion is regulated by a calcium sensor.
  • a separate device - a "citrate calcium monitor" - was developed, which essentially contains two infusion pumps.
  • the citrate and calcium infusion can be specifically controlled.
  • a special algorithm calculates the calcium infusion rate as a function of the blood flow rate and the measured ionized calcium in the patient.
  • the object of the present invention is to improve the detection of the ion concentration of the blood in the implementation and monitoring of local citrate-anticoagulated extracorporeal blood purification.
  • Patient safety is in the foreground.
  • reliable determination and careful monitoring of specific blood parameters - primarily the calcium ion concentration of the blood - and the resulting strict and automated control of citrate and substitution medium delivery rates are of paramount importance.
  • the problems that are specific to the prior art can be solved in a simple manner.
  • the invention brings particularly great advantages in terms of patient safety. Due to the continuous data acquisition, the dosage of the substitution medium can be set in very small time intervals.
  • the dosage of the citrate and the substitution medium takes place taking into account a target value or target value range which can be specified downstream of the citrate feeding point.
  • the target value or target value range can be specified in the controller and can be set by the user.
  • the target or target range may be changed or re-adjusted at any time during blood purification as needed.
  • the invention thus enables ongoing performance and monitoring of anticoagulation and substitution.
  • the Ca and Mg ions are still present in uncomplexed form and can be quantitatively determined - and naturally also qualitatively - without the need for suppression of the ion-citrate complex as in the prior art cited above.
  • the current measured value at this position in the bloodstream represents the currently determined "current ion concentration of the blood", ie those before the anticoagulation and the blood purification, and thus reflects the current intracorporeal physiological state of the patient at the time of the measurement.
  • the substitution medium is dosed as a function of a comparison between a desired value range and the measured ion concentration. Instead of a setpoint range, a setpoint can also be set.
  • a trend towards an undesirable physiological state can be promptly and very quickly reacted by the system. For example, this allows a very early detection of the development of hypocalcaemia in the patient. Hypocalcemia can be very rapid in certain groups of patients and can be a life-threatening complication within a short time. Furthermore, by measuring the ion concentration of the blood in the blood-side part of the extracorporeal circuit in comparison to the prior art, not only a very close-meshed or continuous, but also - depending on the sensor used - also a very accurate quantification of the ions possible.
  • a further great advantage of this method with regard to patient safety results from the fact that a continuous and accurate measured value acquisition, in contrast to the prior art, can essentially be carried out without a metrological effect on the regional anticoagulation and / or dialysis effectiveness. Due to the low complexity of the control of the method according to the invention compared to the above-cited prior art, citrate anticoagulation can be carried out in a user-friendly and automated manner.
  • the basic idea of the invention is a continuously performed measurement of the ion concentration of the blood and a concomitant ongoing control of the citrate anticoagulation, which can be carried out automatically thanks to the invention.
  • the ion concentration of the blood is not determined indirectly as in the above-cited prior art on the basis of the ion concentration in the dialysate, but directly on the blood side in extracorporeal blood circulation.
  • continuous is understood according to the invention to be a measurement of the ion concentration of the blood at regular time intervals, the time intervals advantageously being kept sufficiently short in order to monitor the ion concentration sufficiently closely.
  • Sufficient short time intervals are those in which it can be ensured that a development in the direction of a non-physiological condition of the patient can be detected in good time and counteracted.
  • the ion concentration measuring means measures alkaline earth metal ions.
  • the ion concentration measurement means measures calcium ions.
  • the ion concentration measuring means is an ion-sensitive sensor.
  • the ion concentration measuring means is an optical ion-sensitive sensor.
  • the ion concentration measuring means is a fluorescence-based optical ion-sensitive sensor.
  • the ion concentration measuring means is inserted into the extracorporeal blood circulation.
  • the measurement takes place in the blood-side part of the extracorporeal circuit and the ion concentration measuring means - preferably an ion-sensitive sensor - is in contact with the passing blood. Therefore, there are high demands on the nature of the sensor, since it must meet the requirements for sterility, biocompatibility and cost-effectiveness.
  • biocompatibility is understood to mean a biological compatibility between a material - according to the invention the sensor surface - and a biosystem - according to the invention the blood. At the same time, there is a need for accurate and reliable concentration values to be continuously detected by the sensor.
  • the accuracy of the measured values obtained depends on the sensor used. Sensors are already known from the prior art, which meet the above requirements and are for example in the WO 2006/029293 and the US 4,344,438 described.
  • the in the WO 2006/029293 described sensor device is provided, inter alia, especially for extracorporeal blood circuits.
  • Particularly advantageous are also methods and sensor devices that are used in the bloodstream and capture the concentration of specific components based on their optical properties. A description of such a method and a sensor device can be found, for example, in US Pat US 4,344,438 ,
  • a small amount of blood is diverted via at least one bypass line from the extracorporeal blood circuit and at least one ion concentration measuring means is arranged in this bypass line.
  • the requirements in terms of biocompatibility are not limiting in this embodiment, since the small amount of diverted blood after the measurement is no longer returned to the extracorporeal blood circulation, but discarded.
  • the device according to the invention can be expediently provided with additional ion concentration measuring means:
  • an additional ion concentration measuring means is arranged downstream of the citrate feed point and upstream of the dialysis unit.
  • an additional measurement of the ion concentration takes place downstream of the citrate feed point and upstream of the dialysis unit, the measured ion concentration being a control value for the citrate feed rate and being compared as the actual value with a setpoint value and / or setpoint range, and an exceeding of the setpoint value and / or setpoint range an increase the Citratzuchtrate and falls below the setpoint and / or setpoint range causes a decrease in Citratzuchtrate.
  • an additional ion concentration measuring means is arranged downstream of the dialysis unit and upstream of the substitution medium supply point.
  • additional ionic concentration measurement may be performed downstream of the dialysis unit and upstream of the substitution medium delivery site, with the measured ionic concentration being a control of the substitution medium delivery rate.
  • an additional ion concentration measuring means is provided downstream of the substitution medium supply point.
  • an additional measurement of the ion concentration takes place downstream of the substitution medium supply point, wherein the measured ion concentration is a control variable for the substitution medium supply rate and is compared as an actual value with a setpoint range, wherein exceeding the setpoint range, a reduction of the substitution medium supply rate and falls below the Setpoint range causes an increase in the substitution medium supply rate.
  • the possibility that in a plasma circuit, an additional ion concentration measuring means is arranged.
  • the ion concentration can additionally be measured in the plasma cycle, wherein the measured ion concentration is a control value for the Citratzuchtrate and is compared as an actual value with a setpoint and / or setpoint range and exceeding the setpoint and / or setpoint range causes an increase in the Citratzuchtrate and a Fall below the setpoint and / or setpoint range causes a reduction in Citratzuchtrate.
  • one of the ion concentration measuring means delivers a measured value outside of a predefinable setpoint and / or target value range
  • an alarm can be triggered and the supply of the citrate and the substitution medium can be stopped.
  • Any alarm from the metering devices may result in alarming the blood purification system and bring it into a safe state. This alarm can take place, for example, in the form of an acoustic and / or optical signal.
  • the dosing devices for citrate and for the substitution medium and the extracorporeal blood purification system are connected to one another via the control by means of signal connections, the controller being set up for it To include signals supplied by the extracorporeal blood purification system in their regulation.
  • Signals of extracorporeal blood circulation may be, for example, a change in the level of extracorporeal blood flow or dialysate flow, the type of dialyzer / hemofilter used, the set ultrafiltration rate, stopping the blood pump or an alarm causing the extracorporeal blood flow to stop.
  • the level of extracorporeal blood flow [ml / min] is the volume of blood pumped by the blood pump per unit of time.
  • the dosing devices for citrate and for the substitution medium and the extracorporeal blood purification system are connected to one another via the control by means of signal connections, wherein the controller is set up to include their supplied signals of the dosing devices in their regulation.
  • Such signals of the metering devices can indicate, for example, a spent citrate solution or a consumed substitution medium, a clamped hose or the presence of air bubbles in the hose.
  • the controller is adapted to change the citrate delivery rate and / or or the substitution medium feed rate to cause a proportional change in the ultrafiltration amount of the filtration device or propose an operator.
  • the controller may be provided, as already mentioned, that the patient is deprived of liquid (ultrafiltration). The contribution of ultrafiltration to blood purification is insignificant and serves only to remove fluid retention in the patient.
  • the citrate solution used or the substitution medium solution is very low concentration, then in the course of the supply of the citrate or the substitution medium, a larger volume of fluid enters the extracorporeal blood circulation and thus into the patient, which must be removed again by ultrafiltration. In ultrafiltration, the hematocrit may change further.
  • the hematocrit is an important parameter that should be considered in the delivery of the citrate and / or the substitution medium.
  • the ion concentration is measured continuously at regular intervals.
  • the time intervals should be kept as short as possible so that the monitoring and control of citrate anticoagulation is as close as possible. For most applications, a time interval of 30-60 minutes is sufficient.
  • the ion concentration measuring means or sensor system can operate either without or with interruption.
  • the sensor can be recalibrated during the interruption.
  • a close-meshed measured value detection is also made possible by a variant in which the ion concentration of two or more ion-identical ion concentration measuring means is measured alternately or in rotation, wherein a measuring signal is generated at regular time intervals.
  • the measurements can be very closely meshed be carried out as a recalibration of the currently not measuring ion concentration measuring means, for example, by brief rinsing with a calibration solution is possible.
  • the ions can be determined not only quantitatively but also qualitatively.
  • other methods for determining the ion concentration for example a measurement by means of an ionometer, can also be used instead of sensors.
  • the initial calcium ion concentration and the hematocrit are taken into account as parameters in the dosage of the citrate and the substitution solution and the amount of extracorporeal blood flow is a control parameter for the citrate feed rate wherein a change in the level of extracorporeal blood flow causes a proportional change in the citrate delivery rate.
  • the citrate feed rate is the amount of citrate that is introduced into the extracorporeal blood circulation at a citrate feed site per unit time.
  • the citrate feed rate is adjusted and regulated in the course of treatment so that effective anticoagulation is ensured.
  • various parameters are taken into account according to the invention:
  • the initial calcium ion concentration of the patient is that calcium ion concentration that is determined once before the start of blood purification. Starting from this value, the citrate feed rate is set at the beginning of the treatment.
  • the hematocrit is also taken into account as a parameter in the setting of the required citrate dose.
  • the amount of citrate needed for effective anticoagulation is affected by the hematocrit. The reason for this is the fact that citrate can not permeate through the cell membranes of the blood cells and therefore spreads only in the plasma. In patients with low hematocrit, therefore, a higher citrate dose is necessary for effective anticoagulation and vice versa.
  • the hematocrit is determined once prior to the treatment, ie represents the initial hematocrit and is taken into account as a constant factor in the citrate feed rate.
  • the amount of extracorporeal blood flow is a control value for the Citratzubowrate, wherein a change in the amount of extracorporeal blood flow causes a proportional change in Citratzuschreibrate.
  • the citrate delivery rate is coupled to the extracorporeal blood flow via a constant factor such that a change in extracorporeal blood flow causes a change in the citrate delivery rate.
  • the citrate feed rate is also increased.
  • the dosage of the citrate can be adjusted very accurately, if, furthermore, the binding of the calcium ions to blood-occurring proteins is taken into account as a parameter in the dosage of the citrate.
  • the binding of the calcium ions to citrate is influenced by the proteins occurring in the blood, in particular albumin. It comes to the formation of protein-calcium complexes. For the calculation of how many calcium ions are present protein bound, the law of mass action can be used.
  • the citrate feed rate is set taking this parameter into account at the beginning of the treatment.
  • the target value and / or target value range predeterminable downstream of the citrate feeding site represents the calcium ion concentration of the anticoagulated blood which is present between the citrate feeding site and the dialysis unit.
  • the target value and / or target range is usefully the calcium ion concentration at which blood clotting in the filter is effectively prevented.
  • the literature contains target values which, as a limit value for the calcium ion concentration in the anticoagulated blood, are in the range of 0.25 to 0.35 mmol / l [ Kutsogiannis et al. (2000), Am J Kidney Dis, Vol.
  • the calcium ion concentration of the anticoagulated blood in a range between 0.15 - 0.5 mmol / l, and in particular between 0.2 - 0.4 mmol / l is selectable.
  • the target value can be selected individually according to the condition and needs of the patient. For example, it may be necessary for some patients to set the target to 0.15 mmol / L, while for other patients a higher target of up to 0.5 mmol / L is optimal. Ideally To aim for a value of about 0.2 mmol / l, since at this value, the complement activation is greatly reduced.
  • This target value and / or target value range is specified at the beginning of the treatment and can be set by the user. The target and / or target range may be changed and reset as needed during blood purification.
  • the citrate feed rate measured upstream is a control value for the citrate feed rate, the measured ion concentration being compared as the actual value with a setpoint range and exceeding the setpoint Setpoint range causes an increase in the Citratzuchtrate and falling below the setpoint range causes a decrease in Citratzuschreibrate.
  • the ion concentration measured upstream of the citrate feed site - preferably the calcium ion concentration - reflects the patient's current intracorporeal physiological condition.
  • the setpoint range therefore includes ion concentration values that correspond to a physiological state. Of course, undershooting or exceeding the setpoint range can also trigger an alarm.
  • the ion concentration measured upstream of the citrate feeding site is a regulating value for the substitution medium supply rate, the measured ion concentration being compared as actual value with a desired value range Exceeding the setpoint range causes a decrease in the substitution medium supply rate and a fall below the setpoint range causes an increase in the substitution medium supply rate.
  • the citrate clearance and / or the calcium ion clearance of the dialysis unit may be a control variable for the substitution medium delivery rate, wherein an increase in citrate clearance or a decrease in calcium ion clearance causes a decrease in the substitution medium delivery rate, and a decrease in citrate clearance or an increase in the calcium ion clearance causes an increase in the substitution medium delivery rate.
  • the extent of removal of the citrate, the ion-citrate complexes or the calcium ions by the dialysis filter depends on the filter used and on the blood and dialysate flow or the ratio of blood to dialysate flow.
  • the substitution medium which is downstream of the dialysis filter is introduced into the extracorporeal circuit, usually contains predominantly Ca ions (or additionally also Mg ions).
  • the expected citrate clearance and / or calcium ion clearance may be communicated to the citrate anticoagulation system by entering the filter inserted into the system by the operator prior to initiation of treatment.
  • the clearance can be communicated by entering the filter type (High Flux / Low Flux) and the effective membrane area.
  • the filter type High Flux / Low Flux
  • the effective membrane area For the determination of the citrate clearance or the calcium ion clearance, it is essential to communicate the blood and dialysis flow to the citrate monitor.
  • citrate feed rate is taken into account in the control of the substitution medium feed rate, wherein increasing the citrate feed rate causes an increase in the substitution medium feed rate and decreasing the citrate feed rate causes a decrease in the substitution medium feed rate. If the Citratzuzen is interrupted, for example by a pump failure, so the supply of the substitution medium is interrupted.
  • FIG. 1 schematically shown citrate-anticoagulated blood purification method according to the DE 101 14 283 has already been explained in detail above in the description of the prior art.
  • Fig. 2 shows a schematic representation of a preferred embodiment of an automated citrate-anticoagulated blood purification method according to the invention.
  • the blood of the patient 201 passes via an arterial access 201a into the extracorporeal blood circulation 202 with a blood inlet 203 (arterial limb), a blood outlet 204 (venous limb) and an intervening dialysis unit 205 (represented by a dashed border), and flows over one venous access 201b back into the patient.
  • the dialysis unit 205 is essentially composed of a dialysis filter 205 a, a blood pump 209, an air trap with air bubble detector 210 and a controller 206.
  • an additional blood purification element 205b for example a hemofilter, a hemofilter with a closed plasma circuit or an adsorber circuit, may be provided upstream of the dialysis filter 205a.
  • the blood is brought into contact with the dialysis fluid via a semipermeable membrane.
  • the dialysis fluid is usually prepared by the dialysis machine and pumped by means of a Dialysatpumpe 207a via a Dialysatzulauf 207 in the dialysis filter 205a and derived after passage of the dialysis filter 205a via a Dialysatablauf 208 and disposed of.
  • the above-described components 202-210 form a typical embodiment of an extracorporeal blood purification system.
  • Fig.2 further shows a citrate anticoagulation device with a controlled citrate metering device 212 for delivering citrate at a citrate delivery site 213 upstream of the dialysis filter 205a (and blood purification element 205b, if present) and a controlled substitution medium metering device 214 for delivering a substitution medium to a substitution medium Supply point 215 downstream of the dialysis filter 205a.
  • a citrate anticoagulation device with a controlled citrate metering device 212 for delivering citrate at a citrate delivery site 213 upstream of the dialysis filter 205a (and blood purification element 205b, if present) and a controlled substitution medium metering device 214 for delivering a substitution medium to a substitution medium Supply point 215 downstream of the dialysis filter 205a.
  • the citrate metering device 212 comprises a citrate solution container 216, a drop detector 217, a citrate pump 218, a pressure sensor 226, and an air bubble detector 219.
  • the citrate solution either in the form of Na 3 citrate or ACD-A (acid citrate dextrose-A), which also contains citric acid and dextrose in addition to citrate
  • ACD-A acid citrate dextrose-A
  • the blood becomes in its Coagulation inhibited.
  • the citrate solution as is the case, for example, in an ACD-A solution-low concentration, results in a relatively large volume of liquid which enters the extracorporeal blood circulation 202 per unit of time.
  • the substitution medium metering device 214 also includes a reservoir of substitution medium 220, a drop detector 221, a substitution medium pump 222, a pressure sensor 227 and an air bubble detector 223.
  • the substitution medium contains predominantly Ca ions or Ca and Mg ions and is infused into the extracorporeal blood circuit 202 at the Subsidiary Medium Delivery Site 215. A supply of the substitution medium via a separate venous access would also be possible, but is not desirable for safety reasons.
  • the pump speed of the pumps 218, 222 is determined and monitored by means of Hall sensors and incremental sensors integrated in the pumps 218, 222.
  • the measurement of the patient's ion concentration is carried out with an ion concentration measuring means arranged upstream of the citrate feeding point 213, which is located in the in Fig.2
  • a Ca-ion sensor 224 is used with which the Ca ion concentration is measured sensitively and specifically. It is immaterial whether the Ca-ion sensor 224 is arranged downstream or upstream of the blood pump 209.
  • a small amount of blood can be diverted at regular intervals from the extracorporeal blood circuit 202 and supplied to the Ca-ion sensor 224, wherein the blood is discarded after the measurement.
  • a known sensor device could be combined with a biocompatible Ca-ion-sensitive sensor surface.
  • the measurements are carried out at regular time intervals, the time interval being selected so that a trend in the direction of a non-physiological condition of the patient is detected early. For most applications, a time interval of 30-60 minutes is sufficient. In certain patient groups, eg patients with liver diseases, the interval between two consecutive measurements is a maximum of 10 minutes.
  • the two dosing devices 212, 214 and the Ca-ion sensor 224 are connected to a controller 225.
  • the controller 225 is further connected to the controller 206 of the dialysis unit 205.
  • the controller 225 by which the Ca-ion sensor 224 and the two metering devices 212, 214 are connected, and the control of the dialysis unit (eg a Fresenius 4008/5008 dialysis machine). communicate with each other via a control algorithm.
  • the purpose of the controller 225 is to control and regulate the citrate and substitution medium pumps 218, 222, to evaluate the signals from the sensors 224, 226, 227 and detectors 217, 219, 221, 223, to trigger alarms in the event of malfunction, the pumps 218, 222 in case of malfunction, save data and communicate with the blood purification device.
  • citrate-calcium monitor developed at the Danube University Krems (Center for Biomedical Technology) and cited in the prior art can be used.
  • the Citratzuchtrate Q cit is set in consideration of a predetermined in the controller 225 target value, wherein the initial Ca ion concentration of the blood and the initial padophenokrit be taken into account when setting the Citratzuchtrate Q cit and the amount of blood flow is a control variable for the Citratzuchtrate Q cit ,
  • the initial ion concentration of the blood is determined before starting the treatment either by means of the Ca-ion sensor 224 or by means of a blood sample taken.
  • the initial hematocrit is also determined before starting the treatment with a blood sample.
  • the target value and / or target range represents that Ca ion concentration of the anticoagulated blood which is downstream of the citrate supplying site 213 and upstream of the dialysis unit 205, and is suitably that Ca ion concentration at which blood coagulation in the filter is effectively prevented.
  • target values are given which indicate a Ca ion concentration of 0.25 to 0.4 mmol / l. Ideally, a value of approx. 0.2 mmol / l should be aimed for, as the complement activation is strongly reduced at this Ca ion concentration.
  • This target value and / or target value range can be specified in the controller 225 at the beginning of the treatment and can be set by the user. If necessary, the target value and / or target range can be changed and reset at any time during blood purification.
  • the setting of the citrate feed rate Q cit is based on a mathematical model, which is based on the in Fig. 3 illustrated diagram is illustrated.
  • the diagram shows the characteristic field of the Ca-ion depression with citrate, whereby the citrate concentration in the blood C cit_blut [mmol / l] in dependence of the target concentration of the free Ca ions C iCa [mmol / l] in the anticoagulated blood and the initial Hematocrit Hct [%] is shown.
  • the initial Ca-ion concentration of the blood is with very small deviations at 1.2 mmol / l.
  • the hematocrit values are usually in a range between 25 and 50%. The characteristics were obtained from hematocrit values of 0%, 25% and 50%, either by measurement or by calculation.
  • the characteristic curves corresponding to the respective hematocrit values are marked and labeled in the diagram. From the previously derived equations, it is of course possible to calculate any desired characteristic curves C cit-blood as a function of the iCa target concentration G iCa and the Hct.
  • the necessary citrate feed rate Q cit is determined from the depicted family of curves taking into account the level of blood flow. This is illustrated by the following calculation example:
  • the initial hematocrit Hkt is 50% and the target value of the Ca-ion concentration after citrate addition should be 0.2 mmol / l.
  • the citrate feed rate Q cit is - returned Fig. 2 - Adjusted before starting the treatment by adjusting the pump speed of the citrate pump 218 and adapted only to changes in blood flow Q B. If the blood flow Q B does not change, the citrate feed rate Q cit remains the same throughout the treatment. In order to respond to changes in the blood flow Q B , the citrate feed rate Q cit is connected to the blood flow Q B via a constant factor. Stopping the blood pump 209, and thus the blood flow, is detected by the controller 206, communicated therefrom to the controller 225, which causes the citrate pump 218 to stop. As a result, it is prevented in the sense of patient safety that, when the blood pump 209 stops, citrate is further pumped into the extracorporeal blood circuit 202. Likewise, when the citrate feed rate is changed, the control unit 225 initiates a change in the substitution medium feed rate or stops the substitution medium feed rate Blood pump 209 or the citrate pump 218 is stopped stopping the substitution medium pump 222nd
  • the Citratzuchtrate Q is cit not set in dependence of the measured from the Ca-ion sensor 224 Ca-ion concentration.
  • the Ca ion concentration measured by the Ca ion sensor 224 can also be a control variable for the citrate feed rate.
  • the initial substitution medium supply rate Q Ca / Mg is calculated on the basis of the citrate feed rate Q cit and the citrate clearance of the dialysis filter 205 a and regulated as a function of the Ca ion concentration measured by the Ca ion sensor 224 in accordance with the previous rule.
  • the citrate pump 218 is connected via the controller 225 to the substitution medium pump 222 via a factor calculated according to the above provision. If the blood flow is stopped, the control algorithm automatically stops the citrate feed and, as a result, the supply of the substitution medium. This control algorithm is of great importance for maintaining patient safety and, in the event of failure of the blood pump 209, prevents accumulation of citrate or Ca and Mg ions in the extracorporeal blood circulation 202.
  • the Ca ion concentration measured by the Ca ion sensor 224 reflects the current intracorporeal Ca ion level and thus the physiological state of the patient again. As a result, a trend towards an unphysiological state can be recognized. Thus, in case of exceeding or falling below a limit value range, an alarm can be triggered in addition to the regulation of the substitution medium supply rate Q Ca / Mg .
  • citrate clearance at the substitution medium delivery rate is taken into account.
  • Citrate clearance is a feature of the dialysis filter used and is dependent on blood and dialysate flow. Changes in citrate clearance cause a change in the substitution medium delivery rate.
  • the filter type is entered by the operator in the controller 225. Changes in the citrate and dialysate flow are communicated from the blood pump 209 and the dialysate pump 207a to the controller 206 and from there to the controller 225, which in turn causes an adjustment of the substitution medium supply by driving the substitution medium pump 222.
  • Fig. 4 shows a further embodiment of the invention with extensions over the in Fig. 2 illustrated embodiment.
  • the device shown corresponds to that of Fig. 2 unless otherwise stated below.
  • the extensions shown can be used individually or in combination.
  • an additional means for detecting the ion concentration - a Ca-ion sensor 224a - in the extracorporeal blood circuit 202 'between the Citratzuchtstelle 213 and the dialysis unit 205' may be arranged.
  • the dialysis unit 205 ' is composed of the blood pump 209', the dialysis filter 205a 'and the controller 206'.
  • the Ca ion sensor 224a thus measures the Ca ion concentration of the anticoagulated blood before entering the dialysis unit 205 '.
  • the measured value obtained at this position would have to have a value in accordance with the above-defined predefinable target value and / or target value range when the effective anticoagulation is upright.
  • an additional means for detecting the ion concentration - a Ca ion sensor 224b - between the dialysis unit 205 'and the substitution medium supply point 215 may be arranged. To avoid interference with the measurement by any air bubbles present, it is better to place the Ca ion sensor 224 b downstream of the air trap with air bubble detector 210.
  • the Ca-ion sensor 224b determines the Ca-ion concentration after dialysis and thus enables the exact dosage / control of the substitution medium.
  • the additional blood purification element 205b is a hemofilter 205b 'with a closed plasma circulation 229 and a filtrate pump 230.
  • the plasma can be determined, for example, by means of an adsorber or by means of MDS (Microsphere Detoxification System).
  • MDS Microsphere Detoxification System
  • an additional means of detecting the ion concentration - a Ca ion sensor 224c - may be disposed in the plasma loop 229. Due to the good mixing - the plasma circulates more often through the plasma circuit 229 - the Ca ion concentration in the entire plasma circuit 229 is approximately equal and consequently the Ca ion sensor 224c can be positioned anywhere in the plasma circuit 229.
  • the sensors 224a and 224c measure the actual value and control the Citratzucht so that the actual value corresponds to the preset target value.
  • the controller 225 has to check whether the Citratzuchtrate is within a defined range to avoid unwanted overdose.
  • a change in the citrate feed rate Q cit as described above may cause a change in the substitution medium feed rate Q Ca / Mg by driving the subsitium medium pump 222 'from the controller 225'.
  • An increase in the Citratzubowrate cit Q causes an increase in the substitution medium supply rate Q Ca / Mg and a lowering of the Q Citratzuchtrate cit causes a lowering of the substitution medium supply rate Q Ca / Mg.
  • an additional means for detecting the ion concentration - a Ca ion sensor 224d - may be arranged downstream of the substitution medium supply point 215.
  • the measurements of the Ca-ion sensor 224d are used in another embodiment of the citrate anticoagulation for the dosage / control of the substitution medium.
  • the blood should again have physiological Ca and Mg ion values.
  • the measured values obtained by means of the Ca-ion sensor 224d are supplied to the controller 225 'and a control of the substitution medium supply rate Q Ca / Mg corresponding to the above-described Ca-ion sensor 224 (FIG. Fig. 2 ) carried out.
  • a second Ca-ion sensor 224e of the same type may be located upstream of the citrate feed site 213 ( Fig. 4 ).
  • the Ca ion concentration is measured alternately by the two Ca ion sensors 224 ', 224e, one of the sensors being calibrated while the other generates a measurement signal.
  • the additional Ca-ion sensor 224e may also be configured to control the function of the Ca-ion sensor 224 'and to trigger an alarm in the event of a malfunction, eg if the measured values deviate too much from one another.
  • the Ca-ion sensor 224e may operate either with or without interruptions.
  • the Ca-ion sensor 224e may also be sensitive to another type of ion. For example, due to a limit exceeding change in the ratio of the calcium and magnesium ions, with the Ca ion sensor 224 'detecting the Ca ion concentration and the Ca ion sensor 224e detecting the Mg ion concentration, an alarm may be triggered.
  • Fig. 6a-e show different embodiments of Ca ion sensors.
  • these sensors are disposable items that have been placed in the abovementioned positions prior to treatment (see Fig. 4 ) are placed in the extracorporeal blood circulation or plasma circuit and disposed of after treatment.
  • sterilizable sensors can be used.
  • Fig. 6a shows a Ca-ion sensor with a sensor surface 600, which is integrated in a bypass line 601.
  • a small amount of blood is branched off from the extracorporeal blood circuit 606 into the bypass line 601 and directed to the sensor surface 600.
  • the blood sample is branched off by a pump 607.
  • Ca-sensitive molecules-for example Ca-sensitive fluorophores-immobilized on the sensor surface 600 generate a signal corresponding to the Ca ion concentration (fluorescence signal).
  • a change in the calcium concentration in the ion-sensitive fluorophores leads either to a change in the fluorescence intensity or to a change in the fluorescence wavelength.
  • the Ca-ion sensor 224 disposed upstream of the citrate feed site 213 requires anticoagulation due to the low blood flow rates in the bypass line 601. This can be done by injecting anticoagulant via an anticoagulant line 603 into the bypass line 601. The sensor can be calibrated by adding a calibration solution which is introduced into the bypass line 601 via a calibration solution line 604. In the anticoagulant line 603 and the calibration solution line 604, valves 605b, 605c are arranged.
  • Fig. 6b shows another embodiment of a Ca-ion sensor, wherein also a small amount of blood is diverted from the extracorporeal blood circuit 617 via a pump 618 in a bypass line 610 and the blood sample after the measurement in a waste container 611 is collected and discarded.
  • the Ca-sensitive molecules - eg Ca-sensitive fluorophores - are not immobilized on a sensor surface.
  • the Ca-sensitive molecules are mixed with a blood sample anticoagulated with anticoagulant and the signal is detected via a detection window 612.
  • the anticoagulant is added via an anticoagulant line 613 and the Ca-sensitive fluorophores via a fluorophore line 614 to the blood sample in the bypass line 610.
  • the calibration solution is introduced into the bypass line 610 via a calibration solution line 615.
  • the device elements 616a, 616b, 616c, 616d may be either valves or pumps.
  • a further embodiment of a Ca-ion sensor which has a first sensor surface 630 and a second sensor surface 631.
  • Ca-sensitive molecules - for example Ca-sensitive fluorophores - are immobilized, which generate a signal corresponding to the Ca ion concentration (fluorescence signal).
  • a redundant or alternating measurement can be performed.
  • a small amount of blood is diverted from the extracorporeal blood circuit 639 into a bypass line 632.
  • the bypass line 632 splits into two further bypass lines 632a and 632b.
  • bypass line at 632a and 632b are later combined again to a bypass line 632c, which opens into a waste container 633.
  • the bypass lines 632a, 632b can also open directly into the waste container 633 (dashed extensions).
  • the blood passes from the extracorporeal blood circuit 639 by means of a first pump 638a in the bypass line 632 and can further either in both bypass lines 632a and 632b or via a valve 634 to either the bypass line 632a or the bypass line 632b. From there, the blood passes to the respective sensor surface 631, 630. After the measurement, the blood sample is passed into the waste container 633 and discarded.
  • Anticoagulant is introduced via an anticoagulant line 635 by means of a second pump 638b into the bypass line 632.
  • the calibration solution is introduced into the respective bypass lines 632a, 632b via two calibration solution lines 636, 637 by means of two further pumps 638c, 638d.
  • This arrangement has the advantage that a redundant or alternating measurement with only one line branching off from the extracorporeal blood circuit 202 is possible.
  • the valve 634 When the valve 634 is open for both bypass lines 632a, 632b, the blood sample flows over both sensor surfaces 630, 631 at the same time.
  • the valve 634 may also be configured to perform the measurement alternately with the blood sample alternating only into one the bypass lines 632a, 632b and thus to the respective sensor surface 630, 631 can pass.
  • the respective other bypass line 632a, 632b remains closed and the respective sensor surface 630, 631 can be mixed with calibration solution.
  • FIG Fig. 6d Another embodiment of a Ca ion sensor is shown in FIG Fig. 6d shown.
  • the sensor which has a sensor surface 620 with immobilized Ca-sensitive molecules, eg Ca-sensitive fluorophores, is arranged on the inner wall of the extracorporeal blood circulation 622.
  • the advantage of this principle over the execution principles in Fig. 6a, Fig. 6b and Fig. 6c is the direct measurement in the extracorporeal blood circuit 622. There is therefore no need for a bypass line.
  • the blood does not have to be discarded after the measurement, but constantly flows past the inner wall of the extracorporeal blood circulation sensor surface 620.
  • high demands are placed on sterility and biocompatibility and the sensor should be designed so that no calibration during the treatment time is necessary.
  • could also from the WO 2006/029293 known sensor are provided with a Ca-sensitive sensor surface and come according to this sensor principle for use.
  • the Fig. 6e shows a further embodiment of a recalibratable blood-side Ca-ion sensor.
  • the extracorporeal blood circuit 650 divides into two lines 650a, 650b, which later rejoin into one line.
  • the blood can - controlled by the valves 651, 652 - either flow only via one of the lines 650a, 650b or through both lines.
  • a sensor surface 654 is arranged, which according to those in Fig. 6c described sensor surface 620 is executed.
  • the sensor surface 654 is calibrated, the blood flows only via the conduit 650b.
  • the calibration solution is returned to the sensor surface 654 via a calibration solution line 653 and from there again.
  • Two additional valves 655, 656, which are closed during this process, ensure that the calibration solution only reaches the extracorporeal blood circulation in the area of the sensor surface.
  • An alternating measurement is possible if a sensor surface 657 is also arranged in the line 650b.
  • a calibration solution line 658 and two valves 659, 660 are also provided. As the blood flows over one sensor surface, the other sensor surface can be calibrated. For sensor surfaces that do not require recalibration, both sensor surfaces 654, 657 can be measured at the same time.

Landscapes

  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cardiology (AREA)
  • External Artificial Organs (AREA)

Claims (12)

  1. Dispositif de purification extracorporelle de sang soumis à une anticoagulation au citrate, comprenant :
    un système de purification extracorporelle de sang comportant un circuit extracorporel de sang (202, 202'), lequel présente une unité de dialyse (205, 205', 205''), une entrée de sang (203) dans l'unité de dialyse (205, 205', 205'') pour du sang prélevé à partir d'un patient (201) et une sortie de sang (204) à partir de l'unité de dialyse (205, 205', 205'') pour du sang retournant dans le patient (201) ;
    un dispositif de dosage de citrate (212) commandé pour l'amenée de citrate à un point d'amenée de citrate (213) en amont de l'unité de dialyse (205) ;
    un dispositif de dosage de milieu de substitution (214) commandé pour l'amenée d'un milieu de substitution à un point d'amenée de milieu de substitution (215) en aval de l'unité de dialyse (205) ;
    au moins un moyen (224, 224', 224e, 224'') de mesure de la concentration en ions pour la mesure de cations divalents ;
    et
    un dispositif de commande (225, 225', 225''), lequel est relié avec le ou les moyens (224, 224', 224e, 224'') de mesure de concentration en ions ainsi qu'au dispositif de dosage de citrate (212) et au dispositif de dosage de milieu de substitution (214), le dispositif de commande (225, 225', 225'') étant adapté pour réguler le dosage du milieu de substitution en fonction d'une comparaison entre une plage de valeurs de consigne et la concentration en ions mesurée à l'aide du moyen (224, 224', 224e, 224'') de mesure de concentration en ions,
    caractérisé par le fait que
    le moyen (224, 224', 224e, 224'') de mesure de la concentration en ions est adapté pour générer en continu des valeurs de mesure et est disposé en amont du point d'amenée de citrate (213), et le dispositif de commande (225, 225', 225'') est adapté pour effectuer en continu une régulation du dosage du citrate et du milieu de substitution en considération d'une valeur cible prédéterminée ou d'un domaine de valeurs cibles prédéterminé dans le dispositif de commande (225, 225', 225'') en aval du point d'amenée de citrate (213), la valeur cible prédéterminée ou le domaine de valeurs cibles prédéterminé en aval du point d'amenée de citrate (213) étant la concentration en ions calcium à laquelle une coagulation du sang est efficacement empêchée dans un filtre (205a, 205a') associé à l'unité de dialyse (205, 205', 205''), et le moyen (224, 224', 224e, 224'') de mesure de la concentration en ions étant placé dans le circuit extracorporel de sang (202, 202').
  2. Dispositif selon la revendication 1, caractérisé par le fait que le moyen (224, 224', 224e, 224'') de mesure de la concentration en ions mesure les ions alcalino-terreux, les ions alcalino-terreux étant choisis dans un groupe consistant en ions calcium et ions magnésium.
  3. Dispositif selon l'une des revendications 1 ou 2, caractérisé par le fait que le moyen (224, 224', 224e, 224'') de mesure de la concentration en ions est un capteur sensible aux ions, en particulier un capteur optique sensible aux ions.
  4. Dispositif selon l'une des revendications 1 à 3, caractérisé par un moyen supplémentaire (224a) de mesure de la concentration en ions en aval du point d'amenée de citrate (213) et en amont de l'unité de dialyse (205').
  5. Dispositif selon l'une des revendications 1 à 4, caractérisé par un moyen supplémentaire (224b) de mesure de la concentration en ions en aval de l'unité de dialyse (205') et en amont du point d'amenée de milieu de substitution (215).
  6. Dispositif selon l'une des revendications 1 à 5, caractérisé par un moyen supplémentaire (224d) de mesure de la concentration en ions en aval du point d'amenée de milieu de substitution (215).
  7. Dispositif selon l'une des revendications 1 à 6, caractérisé par un circuit de plasma (229) comportant un moyen supplémentaire (224c) de mesure de la concentration en ions.
  8. Dispositif selon l'une des revendications 1 à 7, caractérisé par le fait que les dispositifs de dosage (212'', 214'') pour le citrate et pour le milieu de substitution et le système de purification extracorporelle de sang sont reliés entre eux par l'intermédiaire du dispositif de commande (225'') au moyen de liaisons par signaux, le dispositif de commande (225'') étant adapté pour intégrer dans sa régulation les signaux du système de purification extracorporelle de sang qui lui sont amenés.
  9. Dispositif selon l'une des revendications 1 à 8, caractérisé par le fait que les dispositifs de dosage (212'', 214'') pour le citrate et pour le milieu de substitution et le système de purification extracorporelle de sang sont reliés entre eux par l'intermédiaire du dispositif de commande (225'') au moyen de liaisons par signaux, le dispositif de commande (225'') étant adapté pour intégrer dans sa régulation les signaux des dispositifs de dosage (212'', 214'') qui lui sont amenés.
  10. Dispositif selon l'une des revendications 1 à 9, caractérisé par un dispositif de filtration (205, 205b) du système de purification extracorporelle de sang, les dispositifs de dosage (212, 214) pour le citrate et pour le milieu de substitution et le système de purification extracorporelle de sang étant reliés entre eux par l'intermédiaire du dispositif de commande (225) au moyen de liaisons par signaux, et le dispositif de commande (225) étant adapté, lors d'une modification du débit d'amenée de citrate et/ou du débit d'amenée de milieu de substitution, pour amener une modification proportionnelle de la quantité d'ultrafiltration du dispositif de filtration (200, 205b) ou pour la proposer à un utilisateur.
  11. Dispositif selon l'une des revendications 1 à 10, caractérisé par le fait que la valeur cible représente la concentration en ions calcium du sang anticoagulé et est apte à être choisie dans une plage de 0,15 - 0,5 mmol/l.
  12. Dispositif selon la revendication 11, caractérisé par le fait que la valeur cible est apte à être choisie dans une plage entre 0,2 - 0,4 mmol/l.
EP08782833.1A 2007-08-31 2008-08-28 Procédé servant à déterminer la concentration ionique dans une opération extracorporelle de purification de sang soumis à une anticoagulation au citrate Active EP2200675B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ATA1368/2007A AT505690B1 (de) 2007-08-31 2007-08-31 Verfahren zum erfassen der ionenkonzentration bei citrat-antikoagulierter extrakorporaler blutreinigung
PCT/AT2008/000305 WO2009026603A1 (fr) 2007-08-31 2008-08-28 Procédé servant à déterminer la concentration ionique dans une opération extracorporelle d'épuration de sang soumis à une anticoagulation au citrate

Publications (2)

Publication Number Publication Date
EP2200675A1 EP2200675A1 (fr) 2010-06-30
EP2200675B1 true EP2200675B1 (fr) 2016-02-10

Family

ID=40104702

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08782833.1A Active EP2200675B1 (fr) 2007-08-31 2008-08-28 Procédé servant à déterminer la concentration ionique dans une opération extracorporelle de purification de sang soumis à une anticoagulation au citrate

Country Status (4)

Country Link
US (1) US9278171B2 (fr)
EP (1) EP2200675B1 (fr)
AT (1) AT505690B1 (fr)
WO (1) WO2009026603A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102018112996A1 (de) 2018-05-30 2019-12-05 Voco Gmbh Adstringierende aluminiumfreie Retraktionspaste für den professionellen zahnärztlichen Gebrauch

Families Citing this family (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006086490A1 (fr) 2005-02-07 2006-08-17 Medtronic, Inc. Detecteur de desequilibre ionique
WO2010029401A2 (fr) 2008-09-09 2010-03-18 Gambro Lundia Ab Procédure et dispositif de traitement sanguin extracorporel utilisant une anti-coagulation au citrate
AU2010230239B2 (en) 2009-03-31 2014-08-07 Gambro Lundia Ab A multipart fluid system and a system for regional citrate anticoagulation in an extracorporeal blood circuit
US8845571B2 (en) 2009-06-17 2014-09-30 Fresenius Medical Care Holdings, Inc. Methods of regional citrate anticoagulation dialysis
US9399091B2 (en) 2009-09-30 2016-07-26 Medtronic, Inc. System and method to regulate ultrafiltration
WO2011063347A2 (fr) 2009-11-20 2011-05-26 Pelican Imaging Corporation Capture et traitement d'images au moyen d'un réseau de caméras monolithique équipé d'imageurs hétérogènes
DE102009060668A1 (de) * 2009-12-28 2011-06-30 Fresenius Medical Care Deutschland GmbH, 61352 Vorrichtung und Verfahren zur Überwachung einer extrakorporalen Blutbehandlung
DE102011010406A1 (de) * 2011-02-04 2012-08-09 Fresenius Medical Care Deutschland Gmbh Verfahren zum Steuern einer Blutbehandlungvorrichtung, Steuereinrichtung, Zugabeeinrichtung und Blutbehandlungsvorrichtung
US9456755B2 (en) 2011-04-29 2016-10-04 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9848778B2 (en) 2011-04-29 2017-12-26 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9561316B2 (en) 2011-04-29 2017-02-07 Medtronic, Inc. Intersession monitoring for blood fluid removal therapy
ES2647775T3 (es) 2011-08-02 2017-12-26 Medtronic, Inc. Sistema de hemodiálisis que tiene una trayectoria de flujo con un volumen distensible controlado
US10857277B2 (en) 2011-08-16 2020-12-08 Medtronic, Inc. Modular hemodialysis system
WO2013043761A1 (fr) 2011-09-19 2013-03-28 Pelican Imaging Corporation Détermination de profondeur à partir d'une pluralité de vues d'une scène contenant un crénelage au moyen d'une fusion hypothétique
KR102002165B1 (ko) 2011-09-28 2019-07-25 포토내이션 리미티드 라이트 필드 이미지 파일의 인코딩 및 디코딩을 위한 시스템 및 방법
US9713668B2 (en) 2012-01-04 2017-07-25 Medtronic, Inc. Multi-staged filtration system for blood fluid removal
EP2817955B1 (fr) 2012-02-21 2018-04-11 FotoNation Cayman Limited Systèmes et procédés pour la manipulation de données d'image de champ lumineux capturé
EP2653178A1 (fr) 2012-04-16 2013-10-23 Zentrum für biomedizinische Technologie der Donau- Universität Krems Dispositif de sécurité pour un traitement du sang extracorporel
KR20150023907A (ko) 2012-06-28 2015-03-05 펠리칸 이매징 코포레이션 결함있는 카메라 어레이들, 광학 어레이들 및 센서들을 검출하기 위한 시스템들 및 방법들
WO2014032020A2 (fr) 2012-08-23 2014-02-27 Pelican Imaging Corporation Estimation de mouvement en haute résolution basée sur des éléments à partir d'images en basse résolution capturées à l'aide d'une source matricielle
US9143711B2 (en) 2012-11-13 2015-09-22 Pelican Imaging Corporation Systems and methods for array camera focal plane control
US10905816B2 (en) 2012-12-10 2021-02-02 Medtronic, Inc. Sodium management system for hemodialysis
US11154648B2 (en) 2013-01-09 2021-10-26 Medtronic, Inc. Fluid circuits for sorbent cartridge with sensors
US9713666B2 (en) 2013-01-09 2017-07-25 Medtronic, Inc. Recirculating dialysate fluid circuit for blood measurement
US11565029B2 (en) 2013-01-09 2023-01-31 Medtronic, Inc. Sorbent cartridge with electrodes
US9707328B2 (en) 2013-01-09 2017-07-18 Medtronic, Inc. Sorbent cartridge to measure solute concentrations
US9623164B2 (en) 2013-02-01 2017-04-18 Medtronic, Inc. Systems and methods for multifunctional volumetric fluid control
US10543052B2 (en) 2013-02-01 2020-01-28 Medtronic, Inc. Portable dialysis cabinet
US10010663B2 (en) 2013-02-01 2018-07-03 Medtronic, Inc. Fluid circuit for delivery of renal replacement therapies
US9526822B2 (en) 2013-02-01 2016-12-27 Medtronic, Inc. Sodium and buffer source cartridges for use in a modular controlled compliant flow path
US10850016B2 (en) 2013-02-01 2020-12-01 Medtronic, Inc. Modular fluid therapy system having jumpered flow paths and systems and methods for cleaning and disinfection
US9144640B2 (en) 2013-02-02 2015-09-29 Medtronic, Inc. Sorbent cartridge configurations for improved dialysate regeneration
US9827361B2 (en) 2013-02-02 2017-11-28 Medtronic, Inc. pH buffer measurement system for hemodialysis systems
US9374512B2 (en) 2013-02-24 2016-06-21 Pelican Imaging Corporation Thin form factor computational array cameras and modular array cameras
DE102013104501A1 (de) * 2013-05-02 2014-11-06 B. Braun Avitum Ag Vorrichtung zur extrakorporalen Blutbehandlung
US9898856B2 (en) 2013-09-27 2018-02-20 Fotonation Cayman Limited Systems and methods for depth-assisted perspective distortion correction
WO2015066731A2 (fr) 2013-11-04 2015-05-07 Medtronic, Inc. Procédé et dispositif pour gérer des volumes de fluides dans le corps
WO2015074078A1 (fr) 2013-11-18 2015-05-21 Pelican Imaging Corporation Estimation de profondeur à partir d'une texture projetée au moyen de réseaux d'appareils de prises de vue
US10537875B2 (en) 2013-11-26 2020-01-21 Medtronic, Inc. Precision recharging of sorbent materials using patient and session data
US9884145B2 (en) 2013-11-26 2018-02-06 Medtronic, Inc. Parallel modules for in-line recharging of sorbents using alternate duty cycles
CN105992552B (zh) 2013-11-27 2019-06-18 美敦力公司 精确透析监测及同步系统
WO2015199766A1 (fr) 2014-06-24 2015-12-30 Medtronic, Inc. Ensemble de régénération de dialysat modulaire
WO2015199768A1 (fr) 2014-06-24 2015-12-30 Medtronic, Inc. Ensemble sorbant empilé
EP2959928A1 (fr) * 2014-06-26 2015-12-30 Infomed SA Dispositif d'épuration du sang par circulation extracorporelle
EP3539586B1 (fr) 2014-10-10 2022-08-24 NxStage Medical Inc. Procédés d'équilibrage de flux
EP3015124B1 (fr) 2014-10-31 2017-08-16 B. Braun Avitum AG Système d'anticoagulation de citrate souple pendant un traitement sanguin extracorporel utilisant la précompensation
US9713665B2 (en) 2014-12-10 2017-07-25 Medtronic, Inc. Degassing system for dialysis
US9895479B2 (en) 2014-12-10 2018-02-20 Medtronic, Inc. Water management system for use in dialysis
US10098993B2 (en) 2014-12-10 2018-10-16 Medtronic, Inc. Sensing and storage system for fluid balance
US10874787B2 (en) 2014-12-10 2020-12-29 Medtronic, Inc. Degassing system for dialysis
CN105517490B (zh) * 2015-09-15 2018-08-10 薛迎风 全自动枸橼酸局部抗凝机
WO2017078965A1 (fr) 2015-11-06 2017-05-11 Medtronic, Inc Optimisation de prescription de dialyse pour réduire le risque d'arythmie
JP6646733B2 (ja) * 2016-03-31 2020-02-14 旭化成メディカル株式会社 血液浄化システム、及びそのプライミング方法
JP6953162B2 (ja) * 2016-03-31 2021-10-27 旭化成メディカル株式会社 血液浄化器
US10994064B2 (en) 2016-08-10 2021-05-04 Medtronic, Inc. Peritoneal dialysate flow path sensing
US10874790B2 (en) 2016-08-10 2020-12-29 Medtronic, Inc. Peritoneal dialysis intracycle osmotic agent adjustment
US10898635B2 (en) 2016-07-18 2021-01-26 Nxstage Medical, Inc. Flow balancing devices, methods, and systems
WO2018045102A1 (fr) 2016-08-30 2018-03-08 Nxstage Medical, Inc. Surveillance de paramètres dans des systèmes de traitement médical
US11013843B2 (en) 2016-09-09 2021-05-25 Medtronic, Inc. Peritoneal dialysis fluid testing system
US10981148B2 (en) 2016-11-29 2021-04-20 Medtronic, Inc. Zirconium oxide module conditioning
WO2018159451A1 (fr) * 2017-03-02 2018-09-07 旭化成メディカル株式会社 Dispositif de purification du sang
CN110382017B (zh) * 2017-03-02 2022-04-29 旭化成医疗株式会社 血液净化装置
US10960381B2 (en) 2017-06-15 2021-03-30 Medtronic, Inc. Zirconium phosphate disinfection recharging and conditioning
US11278654B2 (en) 2017-12-07 2022-03-22 Medtronic, Inc. Pneumatic manifold for a dialysis system
US11033667B2 (en) 2018-02-02 2021-06-15 Medtronic, Inc. Sorbent manifold for a dialysis system
US11110215B2 (en) 2018-02-23 2021-09-07 Medtronic, Inc. Degasser and vent manifolds for dialysis
CN111918683A (zh) * 2018-03-30 2020-11-10 旭化成医疗株式会社 血液净化器及其制法
US11213616B2 (en) 2018-08-24 2022-01-04 Medtronic, Inc. Recharge solution for zirconium phosphate
US11378965B2 (en) 2018-11-15 2022-07-05 Toyota Research Institute, Inc. Systems and methods for controlling a vehicle based on determined complexity of contextual environment
US11806457B2 (en) 2018-11-16 2023-11-07 Mozarc Medical Us Llc Peritoneal dialysis adequacy meaurements
US11806456B2 (en) 2018-12-10 2023-11-07 Mozarc Medical Us Llc Precision peritoneal dialysis therapy based on dialysis adequacy measurements
JP2022534151A (ja) * 2018-12-11 2022-07-28 ガンブロ・ルンディア・エービー 局所クエン酸塩抗凝固療法の性能モニタリング
EP3897770A4 (fr) * 2018-12-21 2022-08-17 The UAB Research Foundation Système pour thérapie continue de remplacement rénal
DE102019130432A1 (de) * 2019-11-12 2021-05-12 Fresenius Medical Care Deutschland Gmbh Steuer- oder Regelvorrichtung, User-Interface und Blutbehandlungsvorrichtung zum Ermitteln neuer Einstellwerte
CN113559342B (zh) * 2021-07-28 2024-01-23 东南大学附属中大医院 配方使用量的确定方法、装置、电子设备及存储介质
US11850344B2 (en) 2021-08-11 2023-12-26 Mozarc Medical Us Llc Gas bubble sensor
CN113588579B (zh) * 2021-08-23 2024-03-01 重庆山外山血液净化技术股份有限公司 血液离子浓度探测装置和方法、钙离子浓度探测方法
US11965763B2 (en) 2021-11-12 2024-04-23 Mozarc Medical Us Llc Determining fluid flow across rotary pump
US11944733B2 (en) 2021-11-18 2024-04-02 Mozarc Medical Us Llc Sodium and bicarbonate control
GB2614308A (en) * 2021-12-24 2023-07-05 Kalium Health Ltd Apparatus and method
EP4360667A1 (fr) 2022-10-24 2024-05-01 Gambro Lundia AB Appareil de traitement extracorporel du sang

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19823570A1 (de) * 1998-05-27 1999-12-02 Kfh Kuratorium Fuer Dialyse Un Verfahren und Vorrichtung zum Austausch von Flüssigkeiten und/oder gelöster Substanzen insbesondere bei einer Dialysebehandlung
ATE380563T1 (de) * 2000-07-07 2007-12-15 Fresenius Medical Care De Gmbh Vorrichtung zur hämodialyse
DE10114283C2 (de) * 2000-12-22 2003-04-24 Fresenius Medical Care De Gmbh Verfahren zur Ermittlung der Ionenkonzentration des Blutes eines Patienten bei der citrat-antikoagulierten Hämodialyse und/oder Hämofiltration; Dialysegerät
US7351218B2 (en) * 2002-12-20 2008-04-01 Gambro Lundia Ab Device and process for extracorporeal treatment by citrate anticoagulant
US7169303B2 (en) * 2003-05-28 2007-01-30 Hemocleanse Technologies, Llc Sorbent reactor for extracorporeal blood treatment systems, peritoneal dialysis systems, and other body fluid treatment systems
US7373195B2 (en) * 2004-07-30 2008-05-13 Medtronic, Inc. Ion sensor for long term use in complex medium
US7468033B2 (en) 2004-09-08 2008-12-23 Medtronic Minimed, Inc. Blood contacting sensor
US20070007184A1 (en) * 2005-07-07 2007-01-11 Delphi Technologies, Inc. Specialized sensor-assisted dialysis
US8372025B2 (en) * 2005-09-22 2013-02-12 Baxter International Inc. Automation and optimization of CRRT treatment using regional citrate anticoagulation
US8211048B2 (en) * 2006-02-22 2012-07-03 Henry Ford Health System System and method for delivery of regional citrate anticoagulation to extracorporeal blood circuits

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102018112996A1 (de) 2018-05-30 2019-12-05 Voco Gmbh Adstringierende aluminiumfreie Retraktionspaste für den professionellen zahnärztlichen Gebrauch

Also Published As

Publication number Publication date
US20110208105A1 (en) 2011-08-25
AT505690A1 (de) 2009-03-15
US9278171B2 (en) 2016-03-08
WO2009026603A1 (fr) 2009-03-05
EP2200675A1 (fr) 2010-06-30
AT505690B1 (de) 2012-09-15

Similar Documents

Publication Publication Date Title
EP2200675B1 (fr) Procédé servant à déterminer la concentration ionique dans une opération extracorporelle de purification de sang soumis à une anticoagulation au citrate
DE10114283C2 (de) Verfahren zur Ermittlung der Ionenkonzentration des Blutes eines Patienten bei der citrat-antikoagulierten Hämodialyse und/oder Hämofiltration; Dialysegerät
EP2640439B1 (fr) Dispositif pour atteindre le mieux possible l'objectif de substitution lors de l'ultrafiltration du sang
EP2838579B1 (fr) Dispositif de sécurité pour un traitement du sang extracorporel
EP2203198B1 (fr) Procédé et dispositif de surveillance de l'amenée d'un liquide de substitution pendant un traitement extracorporel du sang
DE60113624T3 (de) Dialysemaschine
EP2714128B1 (fr) Dispositif et procédé pour la détection d'un état de fonctionnement d'un traitement de sang extracorporel
DE60026530T2 (de) Dialyseapparat
EP2783715B1 (fr) Procédé de détection d'une recirculation dans un shunt artérioveineux pendant une hémodialyse et système de dialyse
EP3096808B1 (fr) Dispositif de régulation et de définition du débit de pompes d'assistance circulatoire
EP3431118B1 (fr) Dispositif pour la mise en oeuvre d'une dialyse isonatrique
EP2722064B1 (fr) Procédé d'optimisation de dialyse
DE102008059379B4 (de) Vorrichtung und Verfahren zur invasiven Blutdruckmessung im Gefäßzugang
WO2014044365A1 (fr) Dispositif et procédé permettant d'identifier une recirculation pendant un traitement sanguin extracorporel
EP2792378B1 (fr) Procédé et dispositif de détermination d'une filtration interne pour un traitement extracorporel du sang
EP2696911B1 (fr) Procédé et dispositif destinés à adapter la performance d'épuration dans le domaine des tailles moléculaires intermédiaires en ajustant le flux de substitution
EP2783713B1 (fr) Détection de recirculation par bolus
EP2783714B1 (fr) Procédé et dispositif de détermination d'un état de recirculation
EP3955988A1 (fr) Mesure de recirculation au moyen d'un équilibre de diffusion
EP2735323A1 (fr) Procédé et dispositif de détection d'une puissance de dialyse réduite
EP3795191B1 (fr) Dispositif de traitement du sang à réduction automatique d'un débit de solution de substitution
WO2021219448A1 (fr) Appareil de dialyse comportant un dispositif permettant de déterminer au moins deux paramètres d'hémodialyse
WO2017093553A1 (fr) Solutions d'hémofiltration pour le traitement d'accidents vasculaires cérébraux

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100325

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20121130

REG Reference to a national code

Ref country code: DE

Ref legal event code: R079

Ref document number: 502008013818

Country of ref document: DE

Free format text: PREVIOUS MAIN CLASS: A61M0001340000

Ipc: A61M0001360000

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RIC1 Information provided on ipc code assigned before grant

Ipc: A61M 1/36 20060101AFI20150724BHEP

Ipc: A61M 1/34 20060101ALI20150724BHEP

INTG Intention to grant announced

Effective date: 20150813

RIN1 Information on inventor provided before grant (corrected)

Inventor name: STROBL, KARIN

Inventor name: HARTMANN, JENS

Inventor name: FALKENHAGEN, DIETER

Inventor name: BRANDL, MARTIN

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 774333

Country of ref document: AT

Kind code of ref document: T

Effective date: 20160215

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: GERMAN

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 502008013818

Country of ref document: DE

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20160210

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 9

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160510

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160511

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160613

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160610

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 502008013818

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160831

26N No opposition filed

Effective date: 20161111

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160510

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20160828

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160831

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160831

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 10

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160828

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160828

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160828

REG Reference to a national code

Ref country code: AT

Ref legal event code: MM01

Ref document number: 774333

Country of ref document: AT

Kind code of ref document: T

Effective date: 20160828

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160828

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20080828

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160210

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20230720

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20230720

Year of fee payment: 16

Ref country code: DE

Payment date: 20230720

Year of fee payment: 16